A highly asymmetric synthesis of the O-2-isocephem class of β-lactam antibiotics

Abstract

Starting from D-threonine, an asymmetric synthesis of the dextrorotatory bioactive enantiomer of 3-methyl-7-phenylacetamido-O-2-isocephem was accomplished. The key step, where asymmetric cycloaddition of azidoacetyl chloride to the cinnamylidene Schiff base of protected D-threonine is induced, generates the desired cis-β-lactam in 90% optical yield. The absolute configuration of the final product was confirmed by comparing its antimicrobial activity with that of its corresponding racemate.